We propose to continue and extend our studies on modified amino acids and modified proteins. The results with "model" proteins will then be applied to studies of the interactions between carcinogen substituted proteins and nucleic acids, with particular attention to potential interactions in cell nuclei. The structure determination of ribonuclease, modified with the carcinogen 3-hydroxyxanthine, has now progressed to the point that the positions of substituted tyrosine and methionine moieties are known. This line of research will be extended to include other carcinogens such as polycyclic hydrocarbons and nitrosamines. A suitable tryptophan containing protein will also be included. Modifications by carcinogens of amino acids in nuclear proteins will then be sought in whole animals. Binding of carcinogens and particularly 3-hydroxyxanthine to membranes is now of interest to immunologists in this Institute, and we shall have their collaboration in certain phases of this effort. An amino acid polymer containing covalently linked carcinogen will be synthesized to prepare antibodies specific to carcinogen-linked amino acid moieties. The binding of phorbol ester to chromatin is to be studied with the same techniques as an example of a non-carcinogenic but tumor-promoting agent.